DK173527B1 - Pharmaceutical preparation for the prevention of sexually transmitted diseases - Google Patents
Pharmaceutical preparation for the prevention of sexually transmitted diseases Download PDFInfo
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- DK173527B1 DK173527B1 DK198903402A DK340289A DK173527B1 DK 173527 B1 DK173527 B1 DK 173527B1 DK 198903402 A DK198903402 A DK 198903402A DK 340289 A DK340289 A DK 340289A DK 173527 B1 DK173527 B1 DK 173527B1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
- A61K9/0036—Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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Description
DK 173527 B1DK 173527 B1
Den foreliggende opfindelse angår forebyggelse af sygdomme, der kan overføres seksuelt, såsom og navnlig AIDS.The present invention relates to the prevention of sexually transmitted diseases such as and especially AIDS.
De mest almindelige seksuelt overførte sygdomme skyldes især virus, bakterier, parasit- og fungusorganismer. Mod udviklingen af disse syg-5 domme har man ikke hidtil kendt noget forebyggelsesmiddel med tilstrækkelig effektivitet, som kan frembyde et alternativ til anvendelse af præservativer, hvis mangler og ulemper er velkendte.The most common sexually transmitted diseases are mainly caused by viruses, bacteria, parasite and fungus organisms. Against the development of these diseases, no preventive agent with sufficient efficacy has been known so far which can provide an alternative to the use of preservatives whose deficiencies and disadvantages are well known.
Ganske vist vides det, at forskellige kemiske midler har en vis virksomhed over for smittekim, som er ansvarlige for seksuelt overført 10 sygdomme. Blandt de mest almindeligt anvendte midler kan nævnes dimethyl al kyl benzalkoniumchl or id eller benzalkoniumchlorid og polyoxyethy-lennonylphenol eller nonoxynol 9.Admittedly, it is known that various chemical agents have some effect on infectious germs, which are responsible for sexually transmitted 10 diseases. Among the most commonly used agents are dimethylalkyl benzalkonium chloride or benzalkonium chloride and polyoxyethylenonylphenol or nonoxynol 9.
Disse produkter har imidlertid kun en relativ effektivitet, eftersom dels deres virkningsspektre er snævre, da de kun dækker visse af de 15 smittekim, der er ansvarlige for seksuelt overførte sygdomme, og dels den tid, der er nødvendig, for at de kan virke, er lang og som følge deraf uacceptabel, eftersom det drejer sig om forebyggelse af seksuelt overførte sygdomme.However, these products have only relative efficacy, since their efficacy spectrum is narrow, as they cover only some of the 15 germs that are responsible for sexually transmitted diseases, and partly the time needed for them to work is long and, as a consequence, unacceptable, since it is about the prevention of sexually transmitted diseases.
Det vides for eksempel, at kontamineringen med AIDS-virus kan ind-20 finde sig allerede inden for de allerførste minutter af dets kontakt med sunde slimhinder. Til gengæld indtræffer inaktiveringen af dette virus med benzalkoniumchlorid i en koncentration på 1% først efter en kontakttid på mindst 10 minutter, hvilket efterlader en yderst betydelig og dermed i praksis uacceptabel kontamineringsmulighed.For example, it is known that contamination with the AIDS virus can occur within the very first minutes of its contact with healthy mucous membranes. In turn, the inactivation of this virus with benzalkonium chloride occurs at a concentration of 1% only after a contact time of at least 10 minutes, leaving a highly significant and thus in practice unacceptable contamination possibility.
25 Som følge deraf muliggør anvendelse af de kendte produkter ikke en effektiv forebyggelse af seksuelt overførte sygdomme, selv når de har virucide egenskaber.As a result, use of the known products does not allow for effective prevention of sexually transmitted diseases, even when they have virucidal properties.
I EP-A-0 255 092 beskrives en sammensætning til topisk anvendelse med en spermicid, viricid og desinficerende virkning, som omfatter en 30 delvist prehydratiseret bærer, der er i stand til at absorbere biologiske fluider. Denne absorbtion af biologiske fluider begrænser risikoen for kontaminering med de vira, som de eventuelt indeholder.EP-A-0 255 092 discloses a composition for topical use with a spermicide, viricide and disinfectant which comprises a partially prehydrated carrier capable of absorbing biological fluids. This absorption of biological fluids limits the risk of contamination with the viruses they may contain.
1 GB-A-1 161 484 beskrives på den anden side lugtfjernende og desinficerende præparater, som er anvendelige ved femininhygieine. Der be-35 skrives ikke sammensætninger, som er beregnede til forebyggelse af seksuelt overførte sygdomme. Præparaterne beskrives i dokumentet som indeholdende et baktericidt middel og et blødgøringsmiddel, som blandt andet kan være en siliconeolie.1 GB-A-1 161 484, on the other hand, describes odor-removing and disinfectant preparations useful in feminine hygiene. No compositions are described which are intended to prevent sexually transmitted diseases. The compositions are described in the document as containing a bactericidal agent and a plasticizer which may be, inter alia, a silicone oil.
2 DK 173527 B12 DK 173527 B1
Fra EP-A-0 113 998 er det i øvrigt kendt, at cholsyrederi vater, hovedsagelig deoxycholsyre og dehydrocholsyre, kan anvendes til behandling af virusinfektioner forårsaget af Herpes Simplex I eller II virus.Furthermore, from EP-A-0 113 998 it is known that cholic acid levels, mainly deoxycholic acid and dehydrocholic acid, can be used to treat viral infections caused by Herpes Simplex I or II virus.
Imidlertid drejer det sig der om en terapeutisk virkning og ikke om 5 en præventiv virkning, mens formålet med opfindelsen netop er at tilvejebringe et præventivt middel. Grænsen mellem terapi og forebyggelse er ikke altid helt klar, men forståelse af forskellen mellem disse to virkningsmåder er essentiel her, idet det er valget af den ene eller den anden, som betinger fastlæggelsen af det anvendte farmaceutiske præparat, 10 udførelsen af behandlingen, dens form, den administreringsmåde samt udstrækningen af dens anvendelse. Til forskel fra den præventive virkning, som angår raske individer, frembringer den terapeutiske virkning, såsom den der er tale om i EP-A-0 113 998, sine virkninger på et allerede angrebet individ. I dette tilfælde er det når infektionen er synlig eller 15 i det mindste påviselig og som følge deraf veletableret, at den syge kan ty til et lægemiddel. Det er således muligt meget nøjagtigt at bestemme de steder, der er inficeret med Herpes Simplex I eller II virusset, dér hvor behandlingen skal appliceres, hvis man gør brug af den topiske vej.However, it is a therapeutic effect and not a preventative effect, while the object of the invention is precisely to provide a preventative agent. The boundary between therapy and prevention is not always clear, but understanding the difference between these two modes of action is essential here, as it is the choice of one or the other that depends on the determination of the pharmaceutical composition used, the performance of the treatment, its form. , the mode of administration and the extent of its use. Unlike the preventive effect that concerns healthy individuals, the therapeutic effect, such as the one in EP-A-0 113 998, produces its effects on an already attacked individual. In this case, when the infection is visible or at least detectable and, as a result, it is well established that the patient can resort to a drug. Thus, it is possible to determine very accurately the sites infected with the Herpes Simplex I or II virus, where the treatment should be applied if the topical route is used.
Der kan således i realiteten regnes med to administreringsmåder, 20 den parenterale vej eller den topiske vej forstået som en meget lokaliseret applikation på det præcise sted, hvor infektionen befinder sig.Thus, in reality, two modes of administration, the parenteral route or the topical route, can be counted on as a highly localized application at the exact location of the infection.
I forbindelse med opfindelsen betegner en administration ad topisk vej applikation af et farmaceutisk præparat ikke blot i en zone, der er nøje afgrænset af en erkendt infektion, men derimod i en omfattende, of-25 te kompleks og altid upræcis zone, eftersom den infektion, som man vil komme i forkøbet, som konsekvens er ikke-1okali seret.In the context of the invention, an administration topically refers to the application of a pharmaceutical composition not only in a zone that is precisely delineated by a recognized infection, but in a comprehensive, often complex and always imprecise zone, since the infection, which one will come up with in consequence, as a consequence is non-localized.
Udtrykket "ad topisk vej", som det anvendes i tilfælde af terapi og således i EP-A-0 113 998 (behandling af et præcist, allerede angrebet punkt), må således ikke forveksles med samme udtryk anvendt her i for-30 bindelse med prævention, hvor betydningen som ovenfor anført er helt anderledes.Thus, the term "topical path" as used in the case of therapy and thus in EP-A-0 113 998 (treatment of a precise, already attacked point) must not be confused with the same term used here in connection with birth control, where the meaning as stated above is quite different.
I øvrigt foretrækkes den topiske vej fremfor den parenterale vej i forbindelse med forebyggelse af seksuelt overførte sygdomme på grund af tilstedeværelsen af visse forbindelser, som er nødvendige for en reel 35 effektivitet, men som ikke bør indføres i organismen. De kan således blive toksiske, når de absorberes i betydelige doser og derefter metabo-liseres af organismen.Furthermore, the topical pathway is preferred over the parenteral pathway in the prevention of sexually transmitted diseases due to the presence of certain compounds which are necessary for real effectiveness but which should not be introduced into the organism. Thus, they can become toxic when absorbed in significant doses and then metabolized by the organism.
Det må endelig bemærkes, at i EP-A-0 113 998 er kun virkningen på 3 DK 173527 B1Finally, it should be noted that in EP-A-0 113 998 only the effect on 3 DK 173527 B1
Herpes Simplex I og II virus beskrevet, mens den foreliggende opfindelse angår prævention mod et udstrakt spektrum af virus, der er ansvarlige for seksuelt overførte sygdomme, hvortil hovedkilderne for eksempel er: - Herpes genitalis I og II virus, 5 - HIV I og HIV II AIDS virus, - hepatitis B virus, - papillomavirus (HPV).The herpes Simplex I and II virus described while the present invention relates to the prevention of an extensive spectrum of viruses responsible for sexually transmitted diseases, the main sources of which are, for example: - Herpes genitalis I and II virus, 5 - HIV I and HIV II AIDS virus, - hepatitis B virus, - papillomavirus (HPV).
Med henblik herpå indbefatter den foreliggende opfindelse beskyttelse af udstrakte komplekse zoner.To this end, the present invention includes protection of extended complex zones.
10 Angivelserne i EP-A-0 113 998 animerer imidlertid ikke fagmanden til at anvende et af cholsyrederivaterne: - dels for en effektiv præventiv virkning i talrige timer, som nødvendiggør applikation af et farmaceutisk præparat på ensartet og tilstrækkelig måde over en dårligt afgrænset zone, den være sig sund, men udsat 15 for at blive kontamineret eller angrebet og således udsat for at konta-minere en partner, -dels for et udstrakt spektrum af virus, som svarer til forskellige manifestationer af sådanne som Herpes Simplex og således af meget mere generelt omfang.10 However, the disclosures in EP-A-0 113 998 do not animate the person skilled in the art to use one of the cholic acid derivatives: - in part, for an effective preventive effect for numerous hours which necessitates the application of a pharmaceutical composition in a uniform and sufficient manner over a poorly defined zone, being healthy, but exposed to contamination or attack and thus exposed to contaminating a partner, and partly to an extensive spectrum of viruses corresponding to various manifestations of such as Herpes Simplex and thus of much more general extent.
20 Den foreliggende opfindelse angår således et farmaceutisk præparat, der indeholder én eller flere aktive bestanddele, der er effektive med hensyn til forbyggelse af seksuelt overførste sygdomme.Thus, the present invention relates to a pharmaceutical composition containing one or more active ingredients effective in preventing sexually transmitted diseases.
Den foreliggende opfindelse angår ligeledes et farmaceutisk præparat, som gør det muligt ad topisk vej at beskytte zoner med høj risiko, 25 såsom kvindens vagina.The present invention also relates to a pharmaceutical composition which allows topically protecting high-risk zones such as the woman's vagina.
Vagina er en slimhinde, som fra naturens hård favoriserer passage af stoffer såvel ved emission mod dens ydre som ved absorption mod den indre organisme.Vagina is a mucous membrane which, by nature, favors the passage of substances both by emission towards its exterior and by absorption against the internal organism.
For en effektiv forebyggelse af seksuelt overførte sygdomme bør den 30 eller de aktive bestanddele ikke blive absorberet af organismen navnlig via en vaginalslimhinde.For effective prevention of sexually transmitted diseases, the organism or active ingredient should not be absorbed by the organism in particular via a vaginal mucosa.
Hidtil har man således ikke kunnet anvende visse stoffer til en sådan prævention, selv om de ville være virkningsfulde, eftersom disse stoffer diffunderer hurtigt i organismen.Thus far, some substances have not been used for such contraception, although they would be effective, since these substances diffuse rapidly in the organism.
35 Dette problem løses med den foreliggende opfindelse.This problem is solved with the present invention.
Med henblik herpå angår opfindelsen et farmaceutisk præparat til forebyggelse af seksuelt overførte sygdomme og beregnet til at blive bragt i kontakt med en slimhinde, hvilket præparat er ejendommeligt ved, 4 DK 173527 B1 at det dels indeholder mindst én aktiv bestanddel mod virus eller bakterier, som er ansvarlige for de seksuelt overførte sygdomme, som kan overføres seksuelt, og dels et produkt, der inhiberer penetrationen af den aktive bestanddel gennem slimhinden i kombination med en farmaceu-5 tisk acceptabel bærer, der er egnet til administration af præparatet ad topisk vej.For this purpose, the invention relates to a pharmaceutical composition for the prevention of sexually transmitted diseases and intended to be contacted with a mucosa, which composition is characterized in that it contains at least one active ingredient against viruses or bacteria, which are responsible for the sexually transmitted diseases which can be transmitted sexually, and partly a product which inhibits the penetration of the active ingredient through the mucosa in combination with a pharmaceutically acceptable carrier suitable for topical administration of the composition.
En bedre forståelse af opfindelsen vil kunne fas på grundlag af den følgende detaljerede beskrivelse.A better understanding of the invention may be made on the basis of the following detailed description.
Penetrationsinhibitoren er et inert og atoksisk middel, som er eg-10 net til at danne en isolerende og beskyttende film på slimhinderne eller på huden.The penetration inhibitor is an inert and atoxic agent suitable for forming an insulating and protective film on the mucous membranes or on the skin.
For at være tilstrækkelig må beskyttelsen i øvrigt være effektiv i vaginaåbningen og dække hele slimhinden, hvilket er meget vanskeligt at opnå i betragtning de yderst talrige folder af sidstnævnte.Moreover, to be adequate, the protection must be effective in the vagina opening and cover the entire mucosa, which is very difficult to obtain given the extremely numerous folds of the latter.
15 Det farmaceutiske præparat ifølge opfindelsen indeholder fortrins vis et inert og atoksisk dispergeringsmiddel, der dispergerer den eller de aktive bestanddele med henblik på opnåelse af en ensartet og tilstrækkelig spredning af præparatet.Preferably, the pharmaceutical composition of the invention contains an inert and atoxic dispersant which disperses the active ingredient (s) in order to achieve a uniform and sufficient dispersion of the composition.
Penetrationsinhibitormidlet og dispergeringsmidlet, som er inde-20 holdt i præparatet ifølge opfindelsen, udgøres af samme sammensætning, navnlig af siliconefamilien.The penetration inhibitor agent and the dispersant contained in the composition of the invention are of the same composition, especially of the silicone family.
Det farmaceutiske præparat ifølge opfindelsen indeholder for eksempel et salt af cholsyre som aktiv bestanddel.For example, the pharmaceutical composition of the invention contains a salt of cholic acid as an active ingredient.
Som bekendt er cholsyre en naturlig bestanddel i galde, og såvel 25 den som dens farmaceutisk acceptable salte anvendes inden for terapien som choleretisk middel.As is known, cholic acid is a natural component of bile, and both it and its pharmaceutically acceptable salts are used in the therapy as a choleretic agent.
Fra EP-A-0 285 285 er det kendt at anvende et dispergeringsmiddel, som i dokumentet anføres som værende et middel, der er i stand til at nedsætte overfladespænding i vandige miljøer {tout agent capable 30 d'abaisser la tension interfaciale en milieu aqueux) i kombination med et derivat af cholsyre til behandling af virusinfektioner. Idet man ved, at virusset anvender proteinerne i cellen, som det snylter på, til dannelse af en skal omkring sin nukleinsyrekæde (DNA eller RNA), hviler den i EP-A-0 285 285 postulerede antivirale virkning af dispergeringsmidlet 35 på brydning af skallen på virusset, som, da det nu ikke længere kan invadere andre celler, således destrueres.From EP-A-0 285 285 it is known to use a dispersant, which is stated in the document as being an agent capable of reducing surface tension in aqueous environments {tout agent capable 30 d'abaisser la tension interfaciale en milieu aqueux ) in combination with a derivative of cholic acid for the treatment of viral infections. Knowing that the virus uses the proteins in the cell on which it is spinning to form a shell around its nucleic acid chain (DNA or RNA), the antiviral effect of the dispersant 35 on the break of the skull postulated in EP-A-0 285 285 on the virus, which, as it can no longer invade other cells, is thus destroyed.
Det er vigtigt at præcisere her, at dispergeringsmidlet, hvis virkning er anført ovenfor, indgår i et farmaceutisk præparat, der admini 5 DK 173527 B1 streres af parenteral vej. Det farmaceutiske præparat, som indeholder dispergeringsmidlet, injiceres direkte i blodkredsløbet.It is important to note here that the dispersant, the effect of which is stated above, is included in a pharmaceutical composition administered by parenteral route. The pharmaceutical composition containing the dispersant is injected directly into the bloodstream.
Virkningen af dispergeringsmidlet i kombination med en eller flere aktive bestanddele i det farmaceutiske præparat ifølge opfindelsen er 5 helt anderledes. Her indvirker midlet således ikke direkte på virusset, hvilket er i modsætning til, hvad der er beskrevet i ovennævnte patentskrift.The effect of the dispersant in combination with one or more active ingredients in the pharmaceutical composition of the invention is quite different. Thus, the agent does not directly affect the virus, which is in contrast to what is described in the above-mentioned patent.
Præparatet ifølge opfindelsen er beregnet til administrering ad topisk vej i modsætning til de i EP-A-0 285 285 beskrevne administrerings- 10 måder (parenteral vej og oral vej).The composition of the invention is intended for topical administration as opposed to the administration methods described in EP-A-0 285 285 (parenteral and oral route).
Hovedegenskaben ved det i præparatet ifølge opfindelsen indeholdte filmdannende middel er over hele overfladen af den zone, som ønskes beskyttet, at danne en ensartet og isolerende film, der fungerer som barriere: 15 - den inhiberer penetrationen af den aktive bestanddel til organis men og hindrer denne i at blive metaboli seret; efter spredning giver den den aktive bestanddel tid til at virke; - den hindrer diffusion af virus, som er ansvarlige for seksuelt overførte sygdomme gennem slimhinden. De uønskede virus holdes således i 20 kontakt med den aktive bestanddel, som kan ødelægge dem; - dens isolerende og beskyttende rolle er dobbelt i den forstand, at den dels beskytter en rask kvinde mod en eventuel kontaminering fra en angrebet partner og dels i det tilfælde, hvor kvinden er angrebet, beskytter partneren ved den samme isolerende virkning.The main property of the film-forming agent contained in the composition of the invention is to form a uniform and insulating film which acts as a barrier over the entire surface of the zone which is desired to be protected: 15 - it inhibits and prevents the penetration of the active ingredient into the organism. in being metabolized; after dispersal, it gives the active ingredient time to act; - it prevents the diffusion of viruses responsible for sexually transmitted diseases through the mucosa. Thus, the unwanted viruses are kept in contact with the active ingredient which may destroy them; - its isolating and protective role is dual in the sense that it protects a healthy woman from possible contamination from an attacked partner and, in the case where the woman is attacked, protects the partner by the same isolating effect.
25 Kombinationen af den filmdannende virkning og den dispergerende virkning muliggør ligeledes en spredning over hele overfladen af de folder, som udgør en vagi nal slimhinde.The combination of the film-forming effect and the dispersing effect also allows a spread over the entire surface of the folds which form a vaginal mucosa.
Det i det farmaceutiske præparat ifølge opfindelsen anvendte chol-syresalt er fortrinsvis natriumcholat.The cholesterol salt used in the pharmaceutical composition of the invention is preferably sodium cholate.
30 Natriumcholat er et kraftigt virulent og baktericidt middel. Denne forbindelse er en biologisk substans, som er fri for toksicitet og er aktiv selv i lave koncentrationer. Mængden af natriumcholat, som anvendes i det farmaceutiske præparat ifølge opfindelsen, er med fordel mellem 0,2 og 1,5 vægt% og fortrinsvis mellem 0,25 og 1 vægt% baseret på 35 præparatets samlede vægt.Sodium cholate is a potent virulent and bactericidal agent. This compound is a biological substance that is free of toxicity and is active even at low concentrations. Advantageously, the amount of sodium cholate used in the pharmaceutical composition of the invention is between 0.2 and 1.5% by weight and preferably between 0.25 and 1% by weight based on the total weight of the composition.
Det til opfindelsens formål foretrukne filmdannende og dispergerende middel er dimethylpolysiloxan, som også har en antiadhæsiv virkning, som forstærker filmens isolerende virkning.The film forming and dispersing agent preferred for the purpose of the invention is dimethylpolysiloxane, which also has an anti-adhesive effect which enhances the insulating effect of the film.
6 DK 173527 B1 Mængden af dimethylpolysiloxan i det farmaceutiske præparat ifølge opfindelsen er af størrelsesordenen 10 vægt% af en emulsion af 35% dimethyl polysiloxan baseret på præparatets samlede vægt.The amount of dimethyl polysiloxane in the pharmaceutical composition of the invention is on the order of 10% by weight of an emulsion of 35% dimethyl polysiloxane based on the total weight of the composition.
Det bemærkes, at ifølge opfindelsen er mængden af filmdannende mid-5 del meget betydelig i forhold til mængderne af aktive betanddele.It is noted that according to the invention, the amount of film-forming agent is very significant in relation to the amounts of active ingredient.
Dette skyldes, at man tilstræber dannelse af en film ikke kun over hele udstrækningen af overfladen, som skal beskyttes (hvilken er stor, når det drejer sig om vaginalslimhinden), men ligeledes en tilstrækkelig tæthed til at opnå en så effektiv isolerende barrierevirkning som mu-10 ligt, og dette har to formål: - at formindske (men man ønsker fuldstændigt at forhindre) risici for overførsel af patogene midler såvel ved kilden som ved slimhinden, - at undgå absorption af til filmen knyttede aktive bestanddele via slimhinden og således holde disse aktive bestanddele på plads, dér hvor 15 deres topiske virkning er nødvendig.This is because one seeks to form a film not only over the entire extent of the surface to be protected (which is large in the case of the vaginal mucosa), but also a sufficient density to achieve such an effective insulating barrier effect as 10, and this has two purposes: - to reduce (but one wishes to completely prevent) the risks of transmission of pathogenic agents at both the source and the mucosa, - to avoid absorption of active ingredients attached to the film through the mucosa and thus keep these active constituents in place where their topical effect is needed.
Denne mængde kan fortrinsvis øges snarere end mindskes, eftersom den filmdannende virkning har tendens til at blive øget med koncentrationen.This amount can preferably be increased rather than decreased as the film-forming effect tends to increase with concentration.
Den til opfindelsens formål egnede farmaceutisk acceptable bærer er 20 en klassisk bærer, som er egnet til administration ad topisk vej. Når det drejer sig om beskyttelse af vaginal siimhinder, bør bæreren være egnet til intern og længerevarende anvendelse.The pharmaceutically acceptable carrier suitable for the purpose of the invention is a classic carrier suitable for topical administration. When it comes to protecting vaginal mucous membranes, the carrier should be suitable for internal and prolonged use.
Fagmanden udvælger fortrinsvis en vandig bærer, som tillader adhærens og fortynding med de naturligt forekommende fluider.The skilled person preferably selects an aqueous carrier which permits adherence and dilution with the naturally occurring fluids.
25 I en fordelagtig udførelsesform kan præparatet ifølge opfindelsen blandt andet indeholde en puffer, såsom saltsyre for at kunne indstille pH til 4,7. Denne værdi gør det muligt at respektere vaginal floraen og Doederleinbakterien. Den manglende ødelæggelse af Doederleinbakterien er meget vigtig, da den har væsentlig defensive egenskaber over for geniti-30 al infektioner. Den må således bevares.In an advantageous embodiment, the composition according to the invention may contain, among other things, a buffer such as hydrochloric acid in order to adjust the pH to 4.7. This value makes it possible to respect the vaginal flora and the Doederlein bacterium. The failure to destroy the Doederlein bacterium is very important as it has significant defensive properties against genital infections. It must thus be preserved.
Det farmaceutiske præparat ifølge opfindelsen kan foreligge i form af opløsninger (vaginalduscher), cremer eller geler.The pharmaceutical composition of the invention may be in the form of solutions (vaginal showers), creams or gels.
Fagmanden vil kunne vælge en farmaceutisk acceptabel bærer, som er egnet til den opretholdte præsentation.The person skilled in the art will be able to choose a pharmaceutically acceptable carrier suitable for the sustained presentation.
35 Den form, hvori præparatet ifølge opfindelsen foreligger, er knyt tet til dets anvendelsesmåde. Præparatet bør blandt andet have en vis viskositet tilpasset efter den måde, hvorpå det skal anvendes.The form in which the composition of the invention is present is associated with its mode of use. Among other things, the composition should have a certain viscosity adapted to the way it is to be used.
Til dette formål indeholder det farmaceutiske præparat ifølge op- 7 DK 173527 B1 findelsen yderligere et fortykningsmiddel, som gør det muligt at opnå hensigtsmæsig rheologisk opførsel.For this purpose, the pharmaceutical composition according to the invention further contains a thickener, which makes it possible to obtain appropriate rheological behavior.
Blandt de klassiske fortykningsmidler er det til opfindelsens formål foretrukne præparat hydroxypropylmethyl cellulose, der under handels-5 betegnelsen "Métholose 60 SH 4000" sælges af Société SEPPIC, 70 Avenue des Champs-Élysées, 75008 Paris (Frankrig).Among the classic thickeners, the present invention is a hydroxypropyl methyl cellulose preparation which is sold under the trade name "Métholose 60 SH 4000" by Société SEPPIC, 70 Avenue des Champs-Élysées, 75008 Paris (France).
Denne fortykning gør det muligt at justere viskositeten til den grad, som er bedst egnet til præparatets form (opløsning, creme, gel etc.). Den således opnåede viskositet modificeres ikke kendeligt, når 10 præparatets pH varierer under dets tilberedelse.This thickening makes it possible to adjust the viscosity to the degree best suited to the form of the preparation (solution, cream, gel etc.). The viscosity thus obtained is not appreciably modified when the pH of the composition varies during its preparation.
Vigtigheden af dette middel vil bedre kunne forstås ved hjælp af den senere beskrevne applikation.The importance of this agent can be better understood by the application described later.
De doser, der hyppigst opretholdes i et farmaceutisk præparat ifølge opfindelsen, er således resumeret i tabel I: 15Thus, the doses most frequently maintained in a pharmaceutical composition of the invention are summarized in Table I: 15
TABEL ITABLE I
0,25 til 1 vægt% natriumcholat, 10 vægt% af en emulsion indeholdende 35% dimethylpolysiloxan, 20 4 vægt% hydroxypropylmethyl cellulose, saltsyre i en mængde nødvendig til pH = 4,7, vand i mængde op til 100%.0.25 to 1 wt% sodium cholate, 10 wt% of an emulsion containing 35% dimethylpolysiloxane, 4 wt% hydroxypropylmethyl cellulose, hydrochloric acid in an amount necessary to pH = 4.7, water in an amount up to 100%.
Ifølge en yderligere udførelsesform af opfindelsen kombineres flere 25 aktive bestanddele især for at forstærke natriumcholatets virkning, navnlig over for visse bakterier.According to a further embodiment of the invention, several active ingredients are especially combined to enhance the effect of the sodium cholate, especially against certain bacteria.
Præparatet ifølge opfindelsen kan følgelig indeholde et eller flere virucide og baktericide midler, blandt andet med virkning som spermici-der, i kombination med natriumcholatet og det dispergerende filmdannende 30 middel. Blandt disse virucide, baktericide og spermicide midler vælges fortrinsvis benzalkoniumchlorid og/eller nonoxynol 9.Accordingly, the composition of the invention may contain one or more virucidal and bactericidal agents, inter alia, acting as spermicides, in combination with the sodium cholate and the dispersing film-forming agent. Among these virucidal, bactericidal and spermicidal agents, benzalkonium chloride and / or nonoxynol 9 are preferably selected.
Det skal her bemærkes, at muligheden for at anvende nonoxynol 9 illustrerer fordele opnået med opfindelsen. Nonoxynol 9 kan således udvikle en vis toksicitet, når det trænger ind i organismen i betydelige do-35 ser på grund af dets akkumulering navnlig i nyrerne. Ydermere øges dets kapacitet til at passere gennem en vaginalslimhinde med ca. 80%. Det er således fuldstændig muligt og uden risiko at anvende nonoxynol 9 i et præparat ifølge opfindelsen takket være tilstedeværelsen af den i sole- 8 DK 173527 B1 rende film, som er skabt af det i præparatet indeholdte filmdannende middel, som er en inhibitor og således modsætter sig indtrængningen af den aktive bestanddel i organismen.It should be noted here that the possibility of using nonoxynol 9 illustrates advantages obtained by the invention. Thus, nonoxynol 9 can develop some toxicity when it enters the organism in significant doses due to its accumulation especially in the kidneys. Furthermore, its capacity to pass through a vaginal mucosa is increased by approx. 80%. Thus, it is completely possible and without risk to use nonoxynol 9 in a composition according to the invention thanks to the presence of the film-forming film produced by the film-forming agent contained in the composition which is an inhibitor and thus opposes say the penetration of the active ingredient into the organism.
De anvendte mængder af fortrinsvis mellem 0,5 og 1 vægt% og 0,25 og 5 1 vægt% af henholdsvis benzalkoniumchloridet og nonoxynol 9 baseret på præparatets samlede vægt.The amounts used are preferably between 0.5 and 1% by weight and 0.25 and 5% by weight of the benzalkonium chloride and nonoxynol 9, respectively, based on the total weight of the composition.
Et farmaceutisk præparat, som specielt opfylder opfindelsens formål, indeholder således fortrinsvis de i tabel II nedenfor angivne mængdert 10Thus, a pharmaceutical composition which specifically fulfills the object of the invention preferably contains the amounts set out in Table II below.
TABEL IITABLE II
0,25 til 1 vægt% natriumcholat, 15 0,50 til 1 vægt% benzalkoniumchlorid, 0,25 til 1 vægt% nonoxynol 9, 10 vægt% af en emulsion indeholdende 35% dimethylpolysiloxan, 4 vægt% hydroxypropylmethyl cel lul ose, saltsyre i en mængde nødvendig til pH = 4,7, 20 vand i mængde op til 100%.0.25 to 1 wt% sodium cholate, 0.50 to 1 wt% benzalkonium chloride, 0.25 to 1 wt% nonoxynol 9, 10 wt% of an emulsion containing 35% dimethylpolysiloxane, 4 wt% hydroxypropylmethyl cel lul ose, hydrochloric acid an amount needed for pH = 4.7, 20 water in amount up to 100%.
Et farmaceutisk præparat udformet med de i tabel II ovenfor anførte andele er på grund af sin specificitet specielt egnet til forebyggelse af seksuelt overførte sygdomme og gør det muligt at opnå en meget effek-25 tiv beskyttelse.A pharmaceutical composition formed with the proportions set forth in Table II above is particularly suitable for the prevention of sexually transmitted diseases and because of its specificity, provides a very effective protection.
I realiteten er dets virkning på én gang virucid, spermicid og bak-tericid.In effect, its effect is at once virucid, spermicide and bactericidal.
Det muliggør således en effektiv inaktivering af virus, som er ansvarlige for seksuelt overførte sygdomme, men ligeledes af bakterier og 30 fungi, som også er ansvarlige for seksuelt overførte sygdomme, blandt hvilke kan nævnes:Thus, it enables effective inactivation of viruses responsible for sexually transmitted diseases, but also of bacteria and fungi, which are also responsible for sexually transmitted diseases, among which can be mentioned:
Staphylococus Aureus,Staphylococus Aureus,
Candida Albicans,Candida Albicans,
Streptococus Agalactiae, 35 Neisseria Gonorrhoeae,Streptococus Agalactiae, 35 Neisseria Gonorrhoeae,
Garnella Vaginalis,Garnella Vaginalis,
Trichonomas Vaginalis.Trichonomas Vaginalis.
De tre aktive midler, som er kombineret i præparatet i tabel II, 9 DK 173527 B1 virker på komplementær måde og har således et meget stort virkningspektrum.The three active agents, which are combined in the composition of Table II, function in a complementary manner and thus have a very large spectrum of effect.
Som eksempler kan nævnes nonoxynol 9's effektive virkning på Chlamidia Trachomatis, som dog fremkalder en meget betydelig forstærkning af 5 infektioner, som skyldes Candida Albicans. Benzalkoniumchlorid, som ligeledes er til stede i præparatet, har en meget klar virkning på Candida Albicans.Examples include the effective effect of nonoxynol 9 on Chlamidia trachomatis, which, however, induces a very significant 5-fold increase in infections caused by Candida Albicans. Benzalkonium chloride, which is also present in the composition, has a very clear effect on Candida Albicans.
Til forbyggelse af seksuelt overførte sygdomme kan det farmaceutiske præparat ifølge opfindelsen måske med fordel blive anvendt i kombi-10 nation med en vaginaltampon, såsom den der er beskrevet af opfinderen i FR-A-2 614 525. Denne tampon afhjælper ulemper forbundet med de klassiske tamponer, som anvendes til antikonception: udtagelsesvanskelighed, irritation og mangel på diskretion. Dette skyldes, at der på dens legeme forekommer mindst én reces, der tjener til fastgørelses- og udtagnings-15 anordning.For the prevention of sexually transmitted diseases, the pharmaceutical composition of the invention may advantageously be used in combination with a vaginal tampon such as that described by the inventor of FR-A-2 614 525. This tampon alleviates the disadvantages associated with the classic tampons used for contraception: difficulty with withdrawal, irritation and lack of discretion. This is because there is at least one recess on its body which serves for fastening and removing device.
Med henblik på en fordelagtig udførelsesform af det farmaceutiske præparat ifølge opfindelsen bør tamponen i øvrigt have egenskaber, som svarer til dens sammensætning og dens fremsti 11ingsmåde.For the sake of an advantageous embodiment of the pharmaceutical composition according to the invention, the tampon should otherwise have properties corresponding to its composition and method of preparation.
En tampon anvendt som bærer for det farmaceutiske præparat ifølge 20 opfindelsen til forebyggelse af seksuelt overførte sygdomme udgøres således af et åbentcellet skum som for eksempel et polyurethanetherskum.Thus, a tampon used as a carrier for the pharmaceutical composition of the invention for the prevention of sexually transmitted diseases is constituted by an open cell foam such as a polyurethane ether foam.
Polyurethanetherskummet i en tampon anvendt til opfindelsens formål har fortrinsvis en densitet mellem 15 og 28.The polyurethane ether foam in a tampon used for the purposes of the invention preferably has a density between 15 and 28.
Polyurethanetherskummet har desuden fortrinsvis en brudstyrke mel-25 lem 70 og 150 KPa.Furthermore, the polyurethane ether foam preferably has a breaking strength between 70 and 150 KPa.
Endelig er middeldimensionen af de i poyurethanetherskummet indeholdte celler fortrinsvis mellem 0,67 og 0,53 mm.Finally, the average dimension of the cells contained in the polyurethane ether foam is preferably between 0.67 and 0.53 mm.
I en fordelagtig udførelsesform af opfindelsen fremstilles tamponen på en sådan måde, at den ikke har nogen "hud", det vil sige en mere el -30 ler mindre kontinuert ydre overflade, som praktisk taget er fri for åbne celler.In an advantageous embodiment of the invention, the tampon is manufactured in such a way that it has no "skin", i.e. a more or less clay-less outer surface which is practically free of open cells.
Med henblik herpå udskæres tamponen af en plade af passende tykkelse, som selv er udskåret af en skumblok, som på forhånd er befriet for sin ydre "hud" ved en saveoperation.To this end, the tampon is cut by a plate of appropriate thickness, which is itself cut out of a foam block which is previously freed of its outer "skin" by a sawing operation.
35 Fagmanden vil under hensyntagen til de tidligere anførte kriterier kunne vælge den form og de dimensioner af tamponen, som passer til brugerens anatomi.35 The person skilled in the art will be able to choose the shape and dimensions of the tampon that suit the user's anatomy, taking into account the criteria stated earlier.
Det farmaceutiske præparat ifølge opfindelsen har fortrinsvis form 10 DK 173527 B1 af en vandig gel; vandig af hensyn til den del af legemet, hvor tamponen anvendes. Det drejer således om en intern anvendelse i et meget følsomt område: vaginalslimhinden, som ikke bør blive irriteret eller ødelagt.Preferably, the pharmaceutical composition of the invention is in the form of an aqueous gel; aqueous for the part of the body where the tampon is used. It is thus an internal application in a very sensitive area: the vaginal mucosa, which should not be irritated or damaged.
Desuden er denne gelform perfekt indrettet til retention i tamponen.Furthermore, this gel form is perfectly adapted for retention in the tampon.
5 Præparatet bør for eksempel ikke trænge ud af tamponen i for stor udstrækning under det tryk, der udøves på denne af brugeren for at indføre den i vagina. Tamponen bør i øvrigt blive bevaret og fremfor alt forblive effektiv i et tilstrækkeligt langt tidsrum, i det mindste flere timer, og formen af det farmaceutiske præparat, hvormed tamponen impræg-10 neres bør være en sådan, at den ikke giver en for stor udskillelse af dette under de første minutter af tamponens anbringelse. Anvendelsen af en gel er vigtig, da den afhjælper den ulempe, som ændrer virkningsfuld-heden. Denne gel form tillader ligeledes i kraft af sin specielle viskositet en god kontakt med slimhinderne såvel som en ensartet og tilstræk-15 kelig spredning over disse.For example, the composition should not penetrate the tampon to a great extent under the pressure exerted on it by the user to insert it into the vagina. Incidentally, the tampon should be retained and, above all, remain effective for a sufficiently long period of time, at least several hours, and the form of the pharmaceutical composition with which the tampon is impregnated should be such that it does not cause excessive secretion of the tampon. this during the first minutes of tampon placement. The use of a gel is important as it eliminates the disadvantage which changes the efficacy. This gel form also, by virtue of its special viscosity, allows good contact with the mucous membranes as well as a uniform and sufficient spread over them.
Det foregående understreger vigtigheden af fortykningsmidlets rolle med hensyn til den nødvendige viskositet, som gelen, hvormed tamponen imprægneres, bør have.The foregoing emphasizes the importance of the role of the thickener in the viscosity required of the gel with which the tampon is impregnated.
Mængden af vandig gel ifølge opfindelsen, som er nødvendig for at 20 imprægnere en tampon, afhænger af dennes dimensioner og sammensætning. Imidlertid viser erfaringen, at det er at foretrække, at tamponen ikke er imprægneret fuldstændigt, da der dels sker en udskillelse af en stor mængde gel, når brugeren sammenpresser tamponen for at indføre den i vagina, og dels er behov for at give de naturlige fluider mulighed for at 25 blive absorberet (ved substitution) og blive neutraliseret. Den mængde gel, som er nødvendig for at imprægnere tamponen, viser sig at opfylde ovennævnte betingelser, når den er af størrelsesordenen 25% af tamponens samlede absorptionsvolumen.The amount of aqueous gel of the invention needed to impregnate a tampon depends on its dimensions and composition. However, experience shows that it is preferable that the tampon is not completely impregnated, since a large amount of gel is secreted when the user compresses the tampon to insert it into the vagina and partly the natural fluids are needed. possibility of being absorbed (by substitution) and neutralized. The amount of gel needed to impregnate the tampon is found to meet the above conditions when it is on the order of 25% of the total absorption volume of the tampon.
Hver tampon emballeres individuelt i en vandtæt kapsel.Each tampon is individually packaged in a waterproof capsule.
30 Til en tampon med en diameter på 45 mm og en tykkelse på 20 mm væl ges en kapsel med en indvendig diameter på 45 mm og en højde på 24 mm.30 For a tampon with a diameter of 45 mm and a thickness of 20 mm, select a capsule with an inner diameter of 45 mm and a height of 24 mm.
Det således disponible spillerum passer til imprægneringsmåden ifølge opfindel sen.The clearance available thus fits the impregnation method according to the invention.
Kapslen har en 5 mm stor periferikant for at tillade lukning af 35 kapslen ved fastsvejsning af et låg over kanten.The capsule has a 5 mm peripheral edge to allow closure of the capsule by welding a lid over the edge.
Lukningen lettes ved tilstedeværelsen af det lille spillerum, som forbliver over tamponen på grund af forskellen mellem dimensionerne af kapslen (24 mm) og tamponen (20 mm).The closure is facilitated by the presence of the small clearance which remains above the tampon due to the difference between the dimensions of the capsule (24 mm) and the tampon (20 mm).
11 DK 173527 B111 DK 173527 B1
Kapslen kan være dannet af et materiale af polyvinyl type. Låget på sin side udgøres af et aluminumkompleks, som traditionelt anvendes til lukning af formstofbeholdere.The capsule may be formed of a polyvinyl type material. The lid, in turn, is made up of an aluminum complex, which is traditionally used for closing plastic containers.
Ifølge opfindelsen udføres imprægneringen på følgende måde: 5 Den nødvendige mængde af gelen anbringes på bunden af kapslen. Til en tampon på 45 x 20 mm kræves ca. 5 g gel. Denne fordeler sig så som et fint lag over hele kapslens overflade. Derefter anbringes tamponen på gelen og kapslen lukkes. Gelen trænger ind i tamponen ved kapillarvirkning.According to the invention, the impregnation is carried out as follows: The required amount of the gel is placed on the bottom of the capsule. For a 45 x 20 mm tampon, approx. 5 g of gel. This then spreads like a fine layer over the entire surface of the capsule. Then apply the tampon to the gel and close the capsule. The gel penetrates the tampon by capillary action.
10 Imprægneringstiden er af størrelsesordenen 30 sekunder, mens luk ningen med fordel udføres på nogle sekunder straks efter anbringelse af tamponen, det vil sige før imprægneringen af tamponen egentlig er afsluttet.The impregnation time is of the order of 30 seconds, while the closure is advantageously carried out in a few seconds immediately after application of the tampon, that is, before the impregnation of the tampon is actually completed.
Imprægneringen fuldføres følgelig under de sidste emballeringsope-15 rationer. Med andre ord opnås imprægneringen "på skjult tid".Accordingly, the impregnation is completed during the last packaging operations. In other words, the impregnation is achieved "in a hidden time".
Den modsatte fremgangsmåde, som ville bestå i at anbringe gelen på tamponen og ikke i bunden af kapslen, frarådes, hvis, som det er logisk, det indvendige volumen af kapslen er tæt ved tamponens udvendige volumen. I dette tilfælde er der stor mulighed for, at gelen ved et uheld 20 når ud over kanten af kapslen under dens lukning. Da låget sædvanligvis ved svejsning skal fikseres til denne kant, udgør den mellemliggende gel en hindring for denne svejsning, og dette er så meget desto mere alvorligt, som gelen indeholder en silicone. En ubetydelig mængde gel vil således være tilstrækkelig til fremkalde en ufuldstændig, det vil sige ik-25 ke tæt, lukning.The opposite method, which would consist of applying the gel to the tampon and not the bottom of the capsule, is advised, if, as is logical, the inner volume of the capsule is close to the outer volume of the tampon. In this case, there is a great chance that the gel accidentally reaches beyond the edge of the capsule during its closure. Since the lid usually has to be fixed to this edge during welding, the intermediate gel is an obstacle to this welding and this is all the more serious as the gel contains a silicone. Thus, a negligible amount of gel will be sufficient to induce an incomplete, i.e., not tight, closure.
I øvrigt er sterilisering af tamponen ikke bydende nødvendig som følge af dens høje indhold af virucide og baktericide midler.Incidentally, sterilization of the tampon is not imperative due to its high content of virucidal and bactericidal agents.
Anvendelsen af en tampon imprægneret med flere aktive bestanddele i kombination frembyder i kraft af disses komplementære aktivitet nye for-30 dele, som specielt er egnet til forbyggelse af seksuelt overførte sygdomme .The use of a tampon impregnated with several active ingredients in combination, by virtue of their complementary activity, offers new advantages which are particularly suitable for the prevention of sexually transmitted diseases.
Idet tamponen er forsynet med åbne celler over hele sin overflade, 9ør tamponen det muligt for den vandige gel, hvormed den er imprægneret, at være til stede og aktiv lige fra tamponens applikation med det formål ^ at indføre den i vaginal åbningen og lidt efter lidt dække hele vaginal-slimhinden, efterhånden som den føres frem, betingelser, der er nødvendige for at sikre en sand og øjeblikkelig beskyttelse.As the tampon is provided with open cells all over its surface, the tampon allows the aqueous gel with which it is impregnated to be present and active right from the application of the tampon for the purpose of introducing it into the vaginal opening and little by little. cover the entire vaginal mucosa as it advances, conditions necessary to ensure true and immediate protection.
Den del af den vandige gel, som trænger ud af tamponen under dens 12 DK 173527 B1 indføring, erstattes ved tamponens periferi med den gel, som fra start er indeholdt i cellerne i den centrale zone takket være kommunikationen mellem de åbne celler. Hvad den interne overførsel angår, er mængden af udgående gel ydermere mere betydelig under seksuelt samkvem som følge af 5 de bevægelser, som det involverer, hvilket er særligt fordelagtigt med hensyn til ødelæggelsen af smittekim indeholdt i såvel vaginalmiljøet som i sperma og i spermatozoider.The portion of the aqueous gel which exits the tampon during its insertion is replaced at the periphery of the tampon with the gel initially contained in the cells of the central zone thanks to the communication between the open cells. As far as internal transfer is concerned, the amount of outgoing gel is more significant during sexual intercourse as a result of the movements it involves, which is particularly advantageous in the destruction of the germs of infection contained in both the vaginal environment and in sperm and in spermatozoids.
Den fysiske spredning af gelen frembyder således den fordel at være konstant og regelmæssig, hvilket ikke er muligt at opnå med en sædvanlig 10 tampon. Dette vil forstærke virkningen af dimethyl polys iloxanen, som parallelt med sine dispergeringsegenskaber muliggør dannelse af en beskyttende film over slimhinderne og huden. En isolerende og hydrofob virkning derved er i realiteten knyttet til selve naturen af dimethylpolysi-loxanen, som hører til siliconefamilien.Thus, the physical dispersion of the gel offers the advantage of being constant and regular, which is not achievable with a conventional tampon. This will enhance the effect of the dimethyl polys iloxane, which, in parallel with its dispersing properties, allows the formation of a protective film over the mucous membranes and the skin. An insulating and hydrophobic effect thereby is in fact linked to the very nature of the dimethylpolysyloxane, which belongs to the silicone family.
15 I kraft af at gelen har en lav koncentration af aktive bestanddele, og at det filmdannende middel har en inhiberende virkning på penetrationen af disse bestanddele i organismen, kan gelen ifølge opfindelsen benyttes til en gentagen og langvarig anvendelse.Because the gel has a low concentration of active ingredients and the film-forming agent has an inhibitory effect on the penetration of these components into the organism, the gel of the invention can be used for repeated and prolonged use.
Brugeren kan således forny den imprægnerede tampon så ofte som øn-20 sket. Samme tampon kan efterlades på plads i flere timer uden risiko for at frembringe en irritation af vaginalslimhinden selv i tilfælde af, at den glemmes.Thus, the user can renew the impregnated tampon as often as desired. The same tampon can be left in place for several hours without the risk of causing an irritation to the vaginal mucosa even in the event of it being forgotten.
I øvrigt anbefales det at lade den blive på plads mindst seks timer efter det sidste seksuelle forhold for at sikre den bedst mulige beskyt-25 telse.In addition, it is recommended to leave it in place at least six hours after the last sexual relationship to ensure the best possible protection.
Benzalkoniumchloridets tilstedeværelse i formuleringen i tabel II vil forstærke den eksisterende virkning af natriumcholatet, og risikoen for toksisk choksyndrom vil blive undgået.The presence of benzalkonium chloride in the formulation in Table II will enhance the existing effect of the sodium cholate and the risk of toxic shock syndrome will be avoided.
Det toksiske choksyndrom skyldes en hurtig proliferation af Staphy-30 lococus Aureus, når andre patogene midler ødelægges. Alvorligheden af denne udvikling skyldes, at Staphylococus Aureus fremkalder kraftige toksiner, som meget hurtigt bliver dødelige. Såvel benzalkoniumchlorid som natriumcholat har imidlertid en markant virkning på denne meget farlige smittekim.The toxic shock syndrome is caused by rapid proliferation of Staphy-30 lococus Aureus when other pathogenic agents are destroyed. The severity of this development is due to the fact that Staphylococus Aureus induces powerful toxins, which very quickly become fatal. However, both benzalkonium chloride and sodium cholate have a marked effect on this very dangerous infection germ.
35 Den som tidligere beskrevet imprægnerede tampon giver en dobbelt beskyttelse. For AIDS for eksempel kan flere tilfælde tænkes: - Seksuelt forhold mellem en rask kvinde og en partner, som er erklæret syg eller seropositiv: kvindens organisme isoleres og beskyttes 13 DK 173527 B1 med filmen, som dækker vaginal slimhinden. De aktive bestanddele ødelægger infektiøse midler indeholdt i sperma eller tilført af partneren.35 The tampon, as previously described, provides double protection. For AIDS, for example, several cases may be considered: - Sexual relationship between a healthy woman and a partner who is declared ill or seropositive: the woman's organism is isolated and protected with the film covering the vaginal mucosa. The active ingredients destroy infectious agents contained in semen or supplied by the partner.
- Seksuelt forhold mellem en kvinde, som er erklæret syg eller se-ropositiv og en rask partner: dækningen af vaginalhulen med gelfilmen 5 isolerer slimhinden og de mulige passagepunkter for virus (erosioner, effraktioner). Virusset kan så ikke forlade den angrebne kvindes organisme. Den fra tamponen udstødte gel fikseres ligeledes på den mandlige partners penis, og filmen beskytter ham således ved direkte kontakt og ved sin forbliver på huden.- Sexual relationship between a woman who is declared ill or seropositive and a healthy partner: the coverage of the vaginal cavity with the gel film 5 isolates the mucosa and the possible points of passage of the virus (erosions, effractions). The virus cannot leave the affected woman's organism. The gel ejected from the tampon is also fixed on the male partner's penis, thus protecting the film by direct contact and by staying on the skin.
10 - Seksuelt forhold mellem en kvinde og en partner, som begge er er klæret syge eller seropositive: ved gelens virkning undgås alvorlig re-infektion af seropositive ved gensidig isolering og ødelæggelse af infektiøse midler af de to oprindelser.10 - Sexual relationship between a woman and a partner, both dressed ill or seropositive: by the action of the gel, severe re-infection of seropositive by mutual isolation and destruction of infectious agents of the two origins is avoided.
Den imprægnerede tampon er således specielt egnet til beskyttelse 15 mod AIDS.Thus, the impregnated tampon is particularly suitable for protection against AIDS.
Den imprægnerede tampon, såsom den tidligere beskrevne, kan anvendes til forebyggelse af seksuelt overførte sygdomme ud over de klassiske antikonceptionelle midler (piller, spiraler etc.). Den kan ikke mindst fungere uden risiko for at forskyde trådene i visse spiraler.The impregnated tampon, such as the one previously described, can be used to prevent sexually transmitted diseases in addition to the classic contraceptive agents (pills, spirals, etc.). Not least, it can work without the risk of displacing the threads in certain spirals.
20 Den har desuden den fordel at være diskret. I modsætning til præ servativet mærkes den ikke af parret. Denne faktor er for præservativets vedkommende meget begrænsende med hensyn til udstrækningen af dets anvendelse. Hvad opfindelsen angår bortfalder denne hindring.20 It also has the advantage of being discreet. Unlike the pre-servative, it is not felt by the couple. This factor is very restrictive for the extent of its use. As to the invention, this obstacle lapses.
Ydermere er den imprægnerede tampon disponibel i en oprive!ig em-25 bal lage til engangsbrug, som gør det muligt at beskytte den og konservere den korrekt, og således gør den meget let at bruge.In addition, the impregnated tampon is available in a single-use, rigid, single-use embal 25 ball, which allows it to be protected and preserved properly, making it very easy to use.
Den i det foregående beskrevne anvendelse udgør en specielt favoriseret udnyttelse af det farmaceutiske præparat ifølge opfindelsen, navnlig, men ikke udelukkende, i kampen mod udbredelsen af AIDS.The use described above constitutes a particularly favored use of the pharmaceutical composition of the invention, in particular, but not exclusively, in the fight against the spread of AIDS.
30 Opfindelsen vil nu blive beskrevet mere detaljeret ved hjælp af de følgende eksempler:The invention will now be described in more detail by means of the following examples:
EKSEMPLEREXAMPLES
35 Anvendte produkter: - Natriumcholat forhandlet af le Société CIPEC, 7 rue Lincoln, 75008 Paris, Frankrig.35 Products used: - Sodium cholate sold by le Société CIPEC, 7 rue Lincoln, 75008 Paris, France.
14 DK 173527 B1 - Benzalkoniumchlorid forhandlet under betegnelsen "REWQUAT B501' af la Société SCHERING, 5 rue Le Corbusier, 94150 Rungis, Frankrig.14 DK 173527 B1 - Benzalkonium chloride negotiated under the designation "REWQUAT B501" by la Société SCHERING, 5 rue Le Corbusier, 94150 Rungis, France.
- Nonoxynol 9 forhandlet under betegnelsen "SIHULSOL 930 NP" af la Société SEPPIC, 70 Avenue des Champs-Élysées, 75008 Paris, Frankrig.- Nonoxynol 9 sold under the designation "SIHULSOL 930 NP" by la Société SEPPIC, 70 Avenue des Champs-Élysées, 75008 Paris, France.
5 - Diméthylpolysiloxan forhandlet under betegnelsen "365 MEDICAL GRADE5 - Dimethyl ethyl polysiloxane negotiated under the designation "365 MEDICAL GRADE
EMULSION" af la Société DOW CORNING CORPORATION, Midland, Michigan 48640, USA.EMULSION "by la Société DOW CORNING CORPORATION, Midland, Michigan 48640, USA.
- Hydroxypropylmethyl cel lul ose forhandlet under betegnelsen "METHOLOSE 60 SH 4000" af la Société SEPPIC, 70 Avenue des Champs-Élysées, 75008 10 Paris, Frankrig.- Hydroxypropylmethyl cel lul ose negotiated under the designation "METHOLOSE 60 SH 4000" by la Société SEPPIC, 70 Avenue des Champs-Élysées, 75008 10 Paris, France.
EKSEMPEL IEXAMPLE I
Vaginal tampon imprægneret med vandig gel ifølge formlen i tabel I.Vaginal tampon impregnated with aqueous gel according to the formula in Table I.
1515
Tampon;tampon;
Tamponen består af et polyuretanetherskum med følgende egenskaber: densitet: ca, 22 brudstyrke: ca. 130 KPa 20 middelcelledimension: 0,6 mm.The tampon consists of a polyurethane ether foam having the following properties: density: approx. 22 breaking strength: approx. 130 KPa 20 medium cell dimension: 0.6 mm.
Den måler 45 mm i diameter og har en tykkelse på 20 mm.It measures 45 mm in diameter and has a thickness of 20 mm.
Den har to fordybninger som beskrevet i FR-A-2 614 525.It has two recesses as described in FR-A-2 614 525.
Gel: 25 Til imprægnering af en tampon med ovennævnte egenskaber kræves 5 g gel. (Det samlede absorptionsvolumen af en sådan tampon er 20 g.) Sammensætningen af den anvendte gel er som følger:Gel: 25 To impregnate a tampon with the above properties, 5 g of gel is required. (The total absorption volume of such a tampon is 20 g.) The composition of the gel used is as follows:
Natriumcholat 0,025 g (o,5%) 30 Diméthylpolysiloxan (35% opløsning) 0,50 g (10%)Sodium Cholate 0.025 g (0.5%) Dimethylethyl polysiloxane (35% solution) 0.50 g (10%)
Hydroxypropylmethylcellulose 0,20 g (4%)Hydroxypropyl methylcellulose 0.20 g (4%)
Saltsyre (IN) q.s. til pH = 4,7Hydrochloric acid (IN) q.s. to pH = 4.7
Renset vand q.s. til 5 g 35Purified water q.s. to 5 g 35
Fremstilling af gel: (Denne fremstillingsmåde kan anvendes, uanset hvilke mængder der benyt tes) 15 DK 173527 B1 I en beholder af rustfrit stål (beholder B) opløses natriumcholatet ved omgivelsestemperatur i halvdelen af mængden af renset vand. Derefter tilsættes dimethylpolysiloxanen. Denne opløsning blandes så under omrøring, til der opnås en homogen opløsning. Eftersom produkterne er over-5 fladeaktive, bør blandingen finde sted ved lav omrøringshastighed.Preparation of Gel: (This method can be used regardless of the quantities used) 15 In a stainless steel container (container B), the sodium cholate is dissolved at ambient temperature in half the amount of purified water. Then the dimethylpolysiloxane is added. This solution is then mixed with stirring until a homogeneous solution is obtained. Since the products are surface active, the mixing should take place at low stirring speed.
I en anden rustfri stål beholder med dobbelt væg (beholder A) opvarmes halvdelen af mængden af renset vand til 70°C ved cirkulation af vanddamp gennem kappen. Derefter tilsættes hydroxypropylmethyl cellulose og dispergeres under omrøring til opnåelse af en homogen gel. Denne gel 10 køles derefter til omgivelsestemperatur ved cirkulation af koldt vand gennem beholderens kappe.In another stainless steel double wall container (container A), half the amount of purified water is heated to 70 ° C by circulating water vapor through the casing. Then hydroxypropyl methyl cellulose is added and dispersed with stirring to give a homogeneous gel. This gel 10 is then cooled to ambient temperature by circulating cold water through the casing of the container.
Den i beholder B opnåede opløsning tilsættes gradvist ved omgivel-sestemperatur til den i beholder A fremstillede gel, idet der omrøres til opnåelse af en homogen gel.The solution obtained in container B is gradually added at ambient temperature to the gel prepared in container A, stirring to obtain a homogeneous gel.
15 pH justeres ved tilsætning af en opløsning af IN saltsyre i til strækkelig mængde til opnåelse af et pH på 4,7.The pH is adjusted by adding a solution of 1N hydrochloric acid to a sufficient amount to obtain a pH of 4.7.
Den samlede masse af gelen indstilles til 5 g ved tilsætning af renset vand i tilstrækkelig mængde.The total mass of the gel is adjusted to 5 g by the addition of purified water in sufficient quantity.
20 Imprægnering af tamponen;20 Impregnation of the tampon;
Den ovenfor opnåede gel anbringes i bunden af en kapsel med en indvendig diameter på 46 mm, en højde på 24 mm og en 5 mm stor periferi-kant.The gel obtained above is placed in the bottom of a capsule with an inner diameter of 46 mm, a height of 24 mm and a 5 mm peripheral edge.
Tamponen anbringes på gelen, og denne trænger ind i tamponen ved 25 kapillarvirkning.The tampon is applied to the gel and it penetrates the tampon by capillary action.
Kapslen lukkes ved påsvejsning af et låg på en sådan måde, at den gøres tæt.The capsule is closed by welding a lid in such a way as to close it.
EKSEMPEL II 30EXAMPLE II 30
Vaginaltampon imprægneret med vandig gel ifølge formlen i tabel II.Vaginal tampon impregnated with aqueous gel according to the formula of Table II.
Tampon:tampon:
Den har samme egenskaber som tamponen i eksempel I.It has the same properties as the tampon in Example I.
3535
Gel:gel:
Til imprægnering af tamponen kræves 5 g gel.To impregnate the tampon, 5 g of gel is required.
Sammensætningen af den anvendte gel er som følger: 16 DK 173527 B1The composition of the gel used is as follows: 16 DK 173527 B1
Natriumcholat 0,025 g (0,5%)0.025 g (0.5%)
Benzalkoniumchlorid 0,050 g (1%)0.050 g (1%) of benzalkonium chloride
Nonoxynol 9 0,025 g (0,5%) 5 Dimethylpolysiloxan (35% opløsning) 0,50 g (10%)Nonoxynol 9 0.025 g (0.5%) Dimethylpolysiloxane (35% solution) 0.50 g (10%)
Hydroxypropylmethyl cel lul ose 0,20 g (4%)Hydroxypropyl methyl cellulose 0.20 g (4%)
Saltsyre IN q.s. til pH = 4,7Hydrochloric acid IN q.s. to pH = 4.7
Renset vand q.s. til 5 g 10 (4 til 4,2 g)Purified water q.s. to 5 g 10 (4 to 4.2 g)
Fremstilling af gel:Preparation of gel:
Fremstillingen udførees på samme måde som i eksempel I. Benzalkoniumchlorid og nonoxynol 9 tilsættes samtidig med dimethyl -15 polysiloxanen.The preparation is carried out in the same manner as in Example I. Benzalkonium chloride and nonoxynol 9 are added simultaneously with the dimethyl-15 polysiloxane.
Imprægnering af tampon:Impregnation of tampon:
Imprægneringen udføres som i eksempel I.The impregnation is carried out as in Example I.
20 FARMAKOLOGISKF EGENSKABER20 PHARMACOLOGICAL PROPERTIES
A - virucide egenskaber I en opløsning inficeret med HIV I AIDS virus er der ved bestemme!-25 se af aktiviteten af inverstranskriptase konstateret en inhibering af det enzymatiske middel af virusset: a - med natriumcholat under nedenstående betingelser: 30 ______A - Virucidal Properties In a solution infected with HIV I AIDS virus, upon determination of the activity of inverse transcriptase, an inhibition of the enzymatic agent of the virus was found: a - with sodium cholate under the following conditions: 30 ______
Koncentration af % Inhibering, Behandlingstid natriumcholat % inverstranskriptase 35 0,04 70 15 min.Concentration of% Inhibition, Treatment Time Sodium Cholate% Inverse Transcriptase 35 0.04 70 15 min.
0,25 90 5 min.0.25 90 5 min.
0,50 99 1 min.0.50 99 1 min.
17 DK 173527 B1 b - med gelen, hvis sammensætning er som beskrevet som eksempel II:17 DK 173527 B1 b - with the gel, the composition of which is as described in Example II:
Koncentration af gel % Inhibering, Behandlingstid 5 (vol/vol) inverstranskriptase 10'6 5 10'5 7 10 10'4 99 .3 10 100 mindre end 2 min.Concentration of Gel% Inhibition, Treatment Time 5 (vol / vol) Inverse Transcriptase 10'6 5 10'5 7 10 10'4 99 .3 10 100 Less Than 2 Min.
. 2 10 100 mindre end 2 min.. 2 10 100 less than 2 min.
15 B - Baktericide egenskaber15 B - Bactericidal properties
Gelen, hvis sammensætning er som beskrevet i eksempel II, udviser ved 32°C følgende baktericide aktivitet: 20 __The gel, whose composition is as described in Example II, exhibits the following bactericidal activity at 32 ° C:
Stamme Antiseptisk Nødvendig koncentration kontakttid (vol/vol) 25 Staphylococus Aureus CIP 53127 0,5% 5 min.Strain Antiseptic Required concentration contact time (vol / vol) 25 Staphylococus Aureus CIP 53127 0.5% 5 min.
Candida Albicans CIP 1180.79 5% 5 min.Candida Albicans CIP 1180.79 5% 5 min.
Streptococus Agalactiae CIP 55 118 0,5% 5 min.Streptococus Agalactiae CIP 55 118 0.5% 5 min.
Neisseria Gonorrhoeae CIP 79 18 0,1% 5 min.Neisseria Gonorrhoeae CIP 79 18 0.1% 5 min.
Garnella Vaginalis CIP 7074 0,5% 5 min.Garnella Vaginalis CIP 7074 0.5% 5 min.
30 _30 _
De i denne tabel anførte bakteriestammer repræsenterer arter, som er ansvarlige for vaginal infektioner, som kan overføres seksuelt.The bacterial strains listed in this table represent species responsible for sexually transmitted vaginal infections.
Den minimale antiseptiske koncentration ifølge Pharmacopée Fran-35 caise er 5 % (g/ml) i 15 minutter.The minimum antiseptic concentration according to Pharmacopée Fran-35 caise is 5% (g / ml) for 15 minutes.
18 DK 173527 B1 C - Antiparasitiske egenskaber I en koncentration på 0,5% (g/ml) i vand med en kontakttid på 5 minutter ved 37°C udviser gelen (hvis sammensætning er som beskrevet i et 5 eksempel II) en øjeblikkelig antiparasitisk virkning, som får populationen Trichonomas Vaginalis til at falde med en faktor på mindst 1000.18 DK 173527 B1 C - Antiparasitic Properties At a concentration of 0.5% (g / ml) in water with a contact time of 5 minutes at 37 ° C, the gel (whose composition is as described in an Example II) exhibits an immediate antiparasitic effect which causes the population of Trichonomas Vaginalis to decrease by a factor of at least 1000.
Claims (20)
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-
1989
- 1989-07-07 NO NO892826A patent/NO178843C/en unknown
- 1989-07-10 HU HU893459A patent/HU206634B/en not_active IP Right Cessation
- 1989-07-10 YU YU135789A patent/YU47899B/en unknown
- 1989-07-10 MY MYPI89000940A patent/MY106242A/en unknown
- 1989-07-10 AT AT89401979T patent/ATE97570T1/en not_active IP Right Cessation
- 1989-07-10 AR AR89314348A patent/AR243381A1/en active
- 1989-07-10 DK DK198903402A patent/DK173527B1/en not_active IP Right Cessation
- 1989-07-10 IL IL9091089A patent/IL90910A/en not_active IP Right Cessation
- 1989-07-10 ES ES89401979T patent/ES2062065T3/en not_active Expired - Lifetime
- 1989-07-10 FI FI893340A patent/FI101595B1/en not_active IP Right Cessation
- 1989-07-10 DE DE89401979T patent/DE68910892T2/en not_active Expired - Fee Related
- 1989-07-10 UA UA4614544A patent/UA26124A/en unknown
- 1989-07-10 EP EP89401979A patent/EP0351301B1/en not_active Expired - Lifetime
- 1989-07-10 MA MA21844A patent/MA22036A1/en unknown
- 1989-07-10 CA CA000605271A patent/CA1341304C/en not_active Expired - Fee Related
- 1989-07-10 RU SU4614544/14A patent/RU2065742C1/en not_active IP Right Cessation
- 1989-07-10 MX MX016734A patent/MX170801B/en unknown
- 1989-07-10 TN TNTNSN89074A patent/TNSN89074A1/en unknown
- 1989-07-10 PT PT91108A patent/PT91108B/en not_active IP Right Cessation
- 1989-07-10 IE IE221889A patent/IE63115B1/en not_active IP Right Cessation
- 1989-07-11 NZ NZ229891A patent/NZ229891A/en unknown
- 1989-07-11 KR KR1019890009850A patent/KR0143231B1/en not_active IP Right Cessation
- 1989-07-11 OA OA59610A patent/OA09123A/en unknown
- 1989-07-11 BR BR898903523A patent/BR8903523A/en not_active IP Right Cessation
- 1989-07-11 CZ CS894238A patent/CZ280722B6/en not_active IP Right Cessation
- 1989-07-11 CN CN89104829A patent/CN1035038C/en not_active Expired - Lifetime
- 1989-07-11 ZA ZA895263A patent/ZA895263B/en unknown
- 1989-07-11 DD DD89330678A patent/DD283932A5/en not_active IP Right Cessation
- 1989-07-11 JP JP1177278A patent/JPH0774164B2/en not_active Expired - Fee Related
- 1989-07-11 TR TR00603/89A patent/TR28353A/en unknown
- 1989-07-11 SK SK4238-89A patent/SK423889A3/en unknown
- 1989-07-11 PL PL89280531A patent/PL161848B1/en unknown
- 1989-07-11 AP APAP/P/1989/000133A patent/AP108A/en active
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1992
- 1992-12-22 US US07/995,522 patent/US5439685A/en not_active Expired - Lifetime
-
1993
- 1993-02-25 LV LVP-93-140A patent/LV10573B/en unknown
- 1993-12-22 LT LTIP1660A patent/LT3754B/en not_active IP Right Cessation
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1994
- 1994-12-30 MD MD95-0089A patent/MD406C2/en unknown
-
1995
- 1995-08-17 HK HK131095A patent/HK131095A/en not_active IP Right Cessation
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|---|---|---|---|
| B1 | Patent granted (law 1993) | ||
| PBP | Patent lapsed |
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